Stefano Iotti is Professor of Clinical Biochemistry at the
University of Bologna, and since 1990 has contributed to the
development of in vivo magnetic resonance spectroscopy both in
basic research and in diagnostic applications. In 1987 he gained
his master's degree (laurea) in Chemistry at the University of
Modena, and a doctorate (dottore di ricerca) in Biochemistry at the
University of Bologna in 1994. Between 1992 and 1993, at the
Metabolic Magnetic Resonance Research and Computing Center and at
the Department of Biochemistry and Biophysics of the University di
Pennsylvania, Philadelphia (USA), he collaborated on in vivo
research on the role of oxygen in the regulation of oxidative
phosphorylation, combining techniques of MR spectroscopy and
near-infrared spectroscopy (NIRS). Other scientific contributions,
at the ICoCEA laboratory of the CNR in Bologna, have included in
vitro synthesis of new anti-sense oligonucleotides and nucleosides,
obtaining patents for the latter for use as anti-viral
agents.
Formerly the research activity was devoted to the study of
molecular interaction between drugs and oligonucleotides, and to
the synthesis of L-nucleotides in liquid phase. These studies
contributed to elucidate the mechanism by which distamycins binds
to the DNA minor groove and to discover that L-thymidine is
selectively phosphorylated by thymidine kinase of the herpes
simplex virus type 1 and not by the human thymidine kinase.
Then, the research activity moved to the in vivo magnetic resonance
spectroscopy (MRS) to study non invasively the metabolic pathways
in living tissues. The phosphorus MRS (31P-MRS) was employed to
explore in vivo the energetic metabolism functionality of human
brain and skeletal muscle both in physiologic and pathologic
conditions.
The 31P-MRS studies on the kinetics of the of the Pi signal decay
after muscular contraction showed to be related to the mechanisms
of Pi transport into mitochondria. This finding put the basis to
create a new experimental approach to study directly in vivo the
kinetics Pi transport. This allowed to build a model of the
mechanism of Pi transport into mitochondria, which in turn leaded
to find an impairment of the kinetics of Pi transport in the
skeletal muscle of Duchenne/Becker carriers. On the basis of this
finding a new non invasive diagnostic test was proposed to disclose
the carrier status in relatives of Duchenne/Becker patients,
particularly useful when the proband is not available to perform
molecular genetic analysis.
The studies of the kinetics of phosphocreatine re-synthesis after
muscular exercise contributed to create a non invasive method to
assess the functionality of mitochondrial respiration proposing the
31P-MRS as new diagnostic tool for the muscular mitochondrial
pathologies.
The further development of the research on the energetic metabolism
required the design of a qualitative and quantitative chemical
model describing the interactions between the phosphorylated
molecules mainly involved in the energetic pathway and the ions
present in the cellular environment. This model has been used to
build original methods to quantify in vivo by 31P-MRS the cytosolic
pH and the free cytosolic [Mg2+] in human brain and skeletal
muscle.
In addition a relevant body of the research activity by MRS has
been directed to the study of pathogenetic mechanisms and to the
therapy effects of several neuronal and neuromuscular
diseases.
An other important achievement was reached in the study of the role
of oxygen in the regulation of oxidative phosphorylation in
skeletal muscle combining near infrared spectroscopy (NIRS) and
31P-MRS, showing that in normoxic conditions the oxygen
availability is not limiting the oxidative phosphorylation even at
maximal rate of energy requirements.
More recently the research activity has been devoted: i) to the
re-definition of the equilibrium constants of phosphorylated
metabolites involved in the energetic metabolism taking into
account the influence of magnesium measured in vivo by 31P-MR; ii)
to the design and development of quantitative mathematical approach
for the in vivo assessment of tissue thermodynamics; iii) to the
development of an absolute quantification method of the metabolites
detectable by proton magnetic resonance spectroscopy (1H-MRS) in
order to enlarge the diagnostic value of MRS; iv)to the design and
development of new radiofrequency surface coils for MRS equipments
with improved sensitivity and spatial selectivity which resulted in
two co-authored patents.
At present a significant part of the activity is directed to the
study of magnesium homeostasis both in living human tissues by in
vivo 31P-MRS and in vitro in cell culture by confocal microscopy
and fluorimetric techniques using a new class of fluorescent
sensors for Magnesium in Living Cells which are hydroxyquinoline
derivatives recently developed whose improved synthesis has been
recently patented. This research line exploits the partnership with
the Research Centers of APS Argonne (Chicago) and Elettra (Trieste)
for Synchrotron X-ray measurements for the Mg2+ intracellular
mapping of different lines of tumor cells sensitive and resistant
di several anticancer drugs.
Last but not least, in collaboration with prof. Sabatini and Vacca
of the University of Florence, a novel procedure was developed to
simplify the treatment of the thermodynamics of complex systems.
This approach of general applicability avoids the complex
calculations required by the use of the Legendre transformed
thermodynamic properties hitherto considered an obligatory
prerequisite to deal with the thermodynamics of biochemical
reactions.
The procedure proposed can be applied to any biochemical reaction,
making possible to re-unify the two worlds of chemical and
biochemical thermodynamics, which so far have been treated
separately, and represents a new paradigm in the biochemical
thermodynamics.The author of numerous publications, he regularly
acts as a referee for international scientific journals concerned
both with the applications of MR spectroscopy and with basic
biochemistry.
